Antiphospholipid syndrome 238273 220373328 2008-06-19T15:25:56Z DOI bot 6652755 Citation maintenance. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. {{DiseaseDisorder infobox | Name = Antiphospholipid syndrome | ICD10 = {{ICD10|D|68|8|d|65}} ([[ILDS]] D68.810) | ICD9 = | ICDO = | Image = | Caption = | OMIM = 107320 | OMIM_mult = | MedlinePlus = | eMedicineSubj = med | eMedicineTopic = 2923 | DiseasesDB = 775 | MeshID = D016736 | }} '''Antiphospholipid syndrome''' (APS or APLS) or '''antiphospholipid antibody syndrome''' is a disorder of [[coagulation]], which causes blood clots ([[thrombosis]]) in both [[artery|arteries]] and [[vein]]s, as well as pregnancy-related complications such as [[miscarriage]], [[Premature birth|preterm delivery]], or severe [[preeclampsia]]. The syndrome occurs due to the [[autoimmune disorder|autoimmune]] production of [[antibody|antibodies]] against [[phospholipid]] (aPL), a [[cell membrane]] substance. In particular, the disease is characterised by antibodies against [[cardiolipin]] ([[anti-cardiolipin antibodies]]) and [[Apolipoprotein H|β<sub>2</sub> glycoprotein I]]. The term "primary antiphospholipid syndrome" is used when APS occurs in the absence of any other related disease. APS is commonly seen in conjunction with other autoimmune diseases; the term "secondary antiphospholipid syndrome" is used when APS coexists with other diseases such as [[systemic lupus erythematosus]] (SLE). In rare cases, APS leads to rapid organ failure due to generalised thrombosis and a high risk of death; this is termed "catastrophic antiphospholipid syndrome". Antiphospholipid syndrome is sometimes [[eponym|referred to]] as '''Hughes syndrome''' after the [[rheumatology|rheumatologist]] Dr. Graham R.V. Hughes ([[St. Thomas' Hospital]], [[London]], [[United Kingdom|UK]]) who worked at the Louise Coote Lupus Unit at St Thomas' Hospital in London. ==Signs and symptoms== The presence of ''antiphospholipid antibodies'' (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS). Antiphosphilipid syndrome can cause ([[artery|arterial]]/[[vein|venous]]) [[blood clot]]s (in any organ system) or [[pregnancy]]-related complications (especially [[miscarriage]] in the second or third [[trimester]]). In APS patients, the most common venous event is [[deep vein thrombosis]] of the lower extremities (blood clot of the deep veins of the legs) and the most common arterial event is [[stroke]]. Other common findings, although not part of the APS Classification Criteria, are [[thrombocytopenia]] (low [[platelet]] count), heart valve disease, and [[livedo reticularis]] (a [[skin]] condition). Some patients report [[headache]]s and [[migraine]]s. Antiphospholipid syndrome can rarely mimic [[multiple sclerosis]] with an estimated 10% of patients misdiagnosed. Very few patients with primary APS go on to develop [[SLE]]. ==Diagnosis== Antiphospholipid syndrome is tested for in the [[laboratory]] using both liquid phase coagulation assays ([[lupus anticoagulant]]) and solid phase [[ELISA]] assays ([[anti-cardiolipin antibodies]]). Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Thus genetic thrombophilia screening can consist of: * Further studies for [[Factor V Leiden]] variant and the [[thrombin|prothrombin mutation]], [[Factor VIII]] levels, [[MTHFR]] mutation. * Levels of [[protein C]], free and total [[protein S]], [[Factor VIII]], [[antithrombin]], [[plasminogen]], [[tissue plasminogen activator]] (TPA) and [[plasminogen activator inhibitor-1]] (PAI-1) The testing of antibodies to the possible individual targets of aPL such as [[Apolipoprotein H|β<sub>2</sub> Glycoprotein 1]] and [[antiphosphatidyl serine]] is currently under debate as testing for anticardiolipin appears to be currently sensitive and specific for diagnosis of APS even though [[cardiolipin]] is not considered an [[in vivo]] target for antiphospholipid antibodies. ===Lupus anticoagulant=== This is tested for by using a minimum of two coagulation tests that are phospholipid sensitive this is due to the heterogeneous nature of the [[lupus anticoagulant]] antibodies. The patient on initial screening will typically have been found to have a prolonged [[APTT]] that does not correct in an 80:20 mixture with normal human [[Blood plasma|plasma]] (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The APTT (plus 80:20 mix), [[dilute Russell's viper venom time]] (DRVVT), the [[kaolin clotting time]] (KCT), [[dilute thromboplastin time]] {TDT/DTT) or [[Prothrombin time]] (using a lupus sensitive [[thromboplastin]]) are the principal tests used for the detection of [[lupus anticoagulant]]. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion demonstrating persistent positivity to allow a diagnosis of antiphospholipid syndrome. This is to prevent patients with transient positive tests (due to infection etc) being diagnosed as positive. Distinguishing a lupus antibody from a specific coagulation factor inhibitor (eg: [[Factor VIII]]). This is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. The lupus anticoagulant will inhibit all the contact activation pathway antibodies ([[Factor VIII]], [[Factor IX]], [[Factor XI]] and [[Factor XII]]). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iudl (35%) where as a specific factor antibody will rarely give a result higher than 10iudl (10%). Monitoring IV anticoagulant therapy by the [[APTR]] is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of [[Factor Xa]] by [[Antithrombin]] in the presence of [[Heparin]]. ===Anticardiolipin antibodies=== These can be detected using an [[ELISA|enzyme-linked immunosorbent assay]] (ELISA) [[immunology|immunological test]], which screens for the presence of β<sub>2</sub>glycoprotein 1 dependent anticardiolipin antibodies (ACA). A [[Thrombocytopenia|Low platelet count]] and positivity for antibodies against β<sub>2</sub>-glycoprotein 1 or [[phosphatidylserine]] may also be observed in a positive diagnosis. ==Criteria== The diagnosis of APS is made in case of a clinical event (vascular thrombosis or pregnancy event) '''and''' repeated positive tests of aPL performed 12 weeks apart (repeat aPL testing is necessary due to the naturally occurring presence of transient low levels of aPL following infections). The Updated Sapporo APS Classification Criteria are commonly used for APS diagnosis.<ref>Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295-306)</ref> Based on these criteria, APS diagnosis requires: * a) ''Vascular Thrombosis'' (blood clots) in any organ or tissue '''or''' ''Pregnancy Event'' (one or more miscarriages after 10th week of gestation, three or more miscarriages before 10th week of gestation, or one or more premature births before 34th week of gestation due to [[eclampsia]]) '''and''' * b) ''Persistenly (12 weeks apart) Positive aPL'' (lupus anticoagulant test, moderate-to-high titer anticardiolipin antibodies, or moderate-to-high titer β<sub>2</sub>-glycoprotein-I antibodies). The International Consensus Statement is commonly used for Catastrophic APS diagnosis.<ref>{{cite journal |author=Asherson RA, Cervera R, de Groot PG, ''et al'' |title=Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines |journal=Lupus |volume=12 |issue=7 |pages=530–4 |year=2003 |pmid=12892393|doi=10.1191/0961203303lu394oa}}</ref> Based on this statement, Definite CAPS diagnosis requires: * a) Vascular Thrombosis in three or more organs or tissues '''and''' * b) Development of manifestations simultaneously or in less than a week '''and'' * c) Evidence of small vessel thrombosis in at least one organ or tissue '''and''' * d) Laboratory confirmation of the presence of aPL. Some serological tests for syphilis may be positive in aPL-positive patients (aPL bind to the lipids in the test and make it come out positive) although the more specific tests for syphilis that use recombinant antigens will be negative. ==Pathogenesis== Antiphospholipid syndrome is an [[autoimmune disease]], in which "antiphospholipid antibodies" (Anticardiolipin antibodies and Lupus anticoagulant) react against proteins that bind to anionic [[phospholipid]]s on [[plasma membrane]]s. Like many [[autoimmune disease]]s, it is more common in women than in men. The exact [[etiology|cause]] is not known, but activation of the system of coagulation is evident. Clinically important antiphospholipid antibodies (those that arise as a result of the autoimmune process) are associated with thrombosis and vascular disease. The syndrome can be divided into primary (no underlying disease state) and secondary (in association with an underlying disease state) forms. The main target of [[anti-cardiolipin antibodies]] is [[apolipoprotein H]] (commonly referred to as β<sub>2</sub>Glycoprotein 1) and the main target of [[Lupus anticoagulant]] is [[prothrombin]]. Other targets of anti-phospholipid antibodies are protein S, protein C and [[annexin A5]]. The Lupus anticoagulant antibodies are those that show the closest association with thrombosis, those that target β<sub>2</sub>glycoprotein 1 have a greater association with thrombosis than those that target prothrombin. Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (>40 GPLU or MPLU). Patients with both Lupus anticoagulant antibodies and moderate/high titre anticardiolipin antibodies show a greater risk of thrombosis than with one alone. ==Treatment== Often, this disease is treated by giving [[aspirin]] to inhibit platelet activation, and/or [[Warfarin]] as an [[anticoagulant]]. The goal of the [[prophylaxis|prophylactic]] treatment is to maintain the patient's [[Prothrombin time|INR]] between 3.0 - 4.0.<ref>{{cite journal |author=Horton JD, Bushwick BM |title=Warfarin therapy: evolving strategies in anticoagulation |journal=American family physician |volume=59 |issue=3 |pages=635–646 |year=1999 |pmid=10029789 |doi=}}</ref> It is not usually done in patients who have not had any thrombotic symptoms. During [[pregnancy]], low molecular weight [[heparin]] and low-dose [[aspirin]] are used instead of Warfarin because of Warfarin's [[teratogen]]icity. Women with recurrent miscarriage are often advised to take aspirin and to start [[low molecular weight heparin]] treatment after missing a [[menstrual cycle]].{{Fact|date=January 2008}} ==References== {{reflist}} ==Bibliography== * Triona Holden. "Positive Options for Antiphospholipid Antibody Syndrome" ISBN 0-89793-409-1. * Kay Thackray. ''Sticky Blood''. ISBN 1-898030-77-4. A personal account of dealing with the condition. ==External links== *[http://www.apsfa.org APS Foundation of America, Inc.] *[http://www.hughes-syndrome.org Hughes Syndrome Foundation] {{Autoantibodies}} {{Hematology}} [[Category:Blood disorders]] [[Category:Rheumatology]] [[Category:Hematology]] [[Category:Autoimmune diseases]] [[Category:Neurology]] [[Category:Obstetrics]] [[Category:Syndromes]] [[de:Antiphospholipid-Syndrom]] [[es:Síndrome antifosfolípido]] [[fr:Syndrome des antiphospholipides]] [[id:Sindrom antibodi antifosfolipid]] [[nl:Antifosfolipidensyndroom]] [[ja:抗リン脂質抗体症候群]] [[pl:Zespół antyfosfolipidowy]] [[sr:Антифосфолипидни синдром]] [[sv:Antifosfolipidsyndrom]]